María Sáinz

Trends in the consumption of attention deficit hyperactivity disorder medications in Castilla y León (Spain): changes in the consumption pattern following the introduction of extended release methylphenidate

Attention deficit hyperactivity disorder (ADHD) is the most diagnosed behavioural disorder in children and adolescents; prevalence has been estimated around 5%. Studies have shown an increase in the use of ADHD medications during the last years. The aim of the present study was to learn the pattern and the evolution of ADHD medication consumption in Castilla y León (Spain).

HMG CoA Reductase Inhibitors and Impotence Two Case Series from the Spanish and French Drug Monitoring Systems

AbstractObjective: HMG CoA Reductase inhibitors, more commonly called statins, are used in the pharmacological management of hyperlipidaemia. At present, the use of these drugs is increasing worldwide. They have been linked to certain adverse drug reactions, including impotence. The aim of the present study is to explore the basis of the association between statin use and impotence using data from spontaneous reports. Method: We analysed the cases of impotence associated with statins that were collected by the Spanish and French pharmacovigilance systems. We used cases of impotence as a numerator and consumption data as a denominator to estimate the cumulative reported incidence of impotence. Results: Thirty-eight cases of impotence associated with statins have been identified in the database of the Spanish pharmacovigilance system; overall, there was a temporal sequence of events in all cases and the adverse reaction disappeared after drug withdrawal in 93% of the cases. Sixteen patients had also been treated with other drugs. In France, 37 cases were collected. In 85% of these cases recovery from the adverse reaction was observed after drug withdrawal; there was a positive rechallenge in five cases, and 15 patients were receiving other drugs at the same time. No significant differences among reported incidences with different statins were found. Conclusion: Considering the widespread use of this drug class and the under-reporting of this particular reaction it could affect a large number of patients. The reaction seems to be reversible in most of the cases after drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing statins to their patients.

Guillain-Barré syndrome and influenza vaccines: A meta-analysis

Cases of Guillain-Barré syndrome (GBS) have been occasionally associated with influenza vaccines; this possible risk, even if rare, is a matter of much concern. To investigate the strength of this association, a systematic review and a meta-analysis have been conducted; for the purpose, controlled observational studies addressing the risk of GBS associated with different influenza vaccines were sought. We finally selected 39 studies of interest published between 1981 and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both vaccines simultaneously administered, 1); funnel plot did not identify publication bias. At the association between any influenza vaccine - whether seasonal or pandemic - with GBS, the overall relative risk was 1.41 (95% CI, 1.20-1.66). Pandemic vaccines presented a higher risk (RR=1.84; 95% CI, 1.36-2.50) compared to seasonal vaccines (RR=1.22; 95% CI, 1.01-1.48); the latter should be considered as marginally statistically significant. Pandemic adjuvanted vaccines were not found to be related to a higher risk compared to non-adjuvanted vaccines. The results of the present meta-analysis point to a small but statistically significant association between influenza vaccines, particularly the pandemic ones, and GBS, which is consistent with current explanations upon possible mechanisms for this condition to appear.

Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems.

Abstract Antidepressants have been associated with a low incidence of idiosyncratic hepatic injury. Some of them, nefazodone or amineptine, were observed to induce severe hepatic injury and withdrawn from the market. Recently, some cases of this severe condition have been reported in association with agomelatine use. Therefore, the objective of this study is to learn the risk of hepatic damage with agomelatine as compared with other new antidepressants. We took data from the Spanish, French, Italian, and Portuguese pharmacovigilance system databases. A case/noncase approach to assess the strength of the association between whichever antidepressant and hepatotoxicity was performed; cases were defined as reports of hepatotoxicity; noncases were reports of all reactions other than hepatotoxicity. Exposure was the recording of a new antidepressant in a report, whether or not it was suspected of causing the reaction. During the period surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants assessed. They represent 10.3% of all cases collected for these drugs; the corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of hepatotoxicity associated with agomelatine were collected since its introduction until the end of the period studied; they account for a percentage of 14.6. Agomelatine was statistically associated with hepatotoxicity in Spain [reporting odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4–9.7)], France (ROR, 2.4 [95% CI, 1.5–3.7]), and Italy (ROR, 5.1 [95% CI, 1.7–14.0]). Current results support the idea of agomelatine to be related to a higher hepatotoxicity risk. Physicians should consider early discontinuation if the condition is suspected; health authorities should promptly explore the best regulatory actions to be taken.

Gynaecomastia Associated with Proton Pump Inhibitors A Case Series from the Spanish Pharmacovigilance System

AbstractObjective: Proton pump inhibitors (PPIs) are widely used in the management of peptic ulcer and related symptoms. They have been linked to certain endocrine adverse reactions, including gynaecomastia. The aim of the present study is to investigate the association between the use of PPIs and the development of gynaecomastia. Methods: Reports of cases of gynaecomastia that had putatively been induced by PPIs and that had been collected by the Spanish Pharmacovigilance System via the ‘yellow card’ scheme, were analysed. Reporting odds ratios (RORs) were calculated as a measure of disproportionality. Results: Twenty-four cases of gynaecomastia associated with PPIs were identified in the database of the Spanish Pharmacovigilance System. Overall, there was a clear temporal sequence of events in all cases and the adverse effect disappeared after drug withdrawal in most of the cases; 14 patients were also receiving other drugs at the time of the adverse effect. The ROR for omeprazole exposure versus no exposure, but not that for other PPIs, showed a statistically significant elevation (ROR adjusted for age 5.23; 95% CI 3.32, 8.26). Conclusion: Considering the widespread use of PPIs, gynaecomastia may affect a large number of patients. In most cases, the condition seems to be reversible with drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing PPIs to their patients over long periods of time.

No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain

A large number of studies have suggested that being a woman represents a potential risk factor for the development of adverse drug reactions (ADRs). The aim of this study is to further explore the differences between men and women with regard to reported ADRs, particularly those associated with psychotropic drugs. We used spontaneous reports of suspected ADRs collected by Midi‐Pyrénées (France), Veneto (Italy) and Castilla y León (Spain) Regional Pharmacovigilance Centres (January 2007–December 2009). All the reports including a psychotropic medication were selected in a first step; age distribution, seriousness and type of ADRs were compared between men and women. Reports of nonpsychotropic drugs were similarly identified and treated. The absolute number of reports and the proportion, considering population, were higher in women than in men. This was observed for all reports, but was particularly higher for psychotropic drugs (592 vs. 375; P < 0.001) than for nonpsychotropics drugs (5193 vs. 4035; P < 0.001). Antidepressants were the most reported (women, 303; men, 141; P < 0.001); the reporting rates (number of reports divided by exposed patients in the same period, estimated through sales data) for these drugs, however, were not significantly different between women (0.87 cases per 10 000 treated persons per year) and men (0.81 cases per 10 000 treated persons per year). Although there was a higher number of reports of ADRs in women, ADR reporting rates might be similar as highlighted by the case of antidepressants. Antidepressant ADRs in fact were similarly reported in men and in women. Gender differences are sometimes subtle and difficult to explore. International networks, as the one established for this study, do contribute to better analyse problems associated with medications.

Strontium ranelate may cause alopecia

From May 2005 to January 2008, the Spanish pharmacovigilance system received 56 reports in which strontium ranelate, a drug intended for the treatment of osteoporosis, was associated with different adverse reactions; five of them (8.9%) were reports of alopecia (table⇓; figure⇓). From the start of pharmacovigilance activities in Spain in 1982 up to January 2008, 102 540 reports were collected, of which 393 (0.4%) were cases of alopecia; the corresponding reports for postmenopausal women were 39 640, of which 205 (0.5%) cases were of alopecia. Alopecia in case 3 (see table). This was accompanied by some features compatible with …

Heart Rhythm Disturbances Associated With Rupatadine: A Case Series From the Spanish and Portuguese Pharmacovigilance Systems

We searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0–10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4–6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbances.

Emergency contraceptive pill safety profile. Comparison of the results of a follow-up study to those coming from spontaneous reporting

The emergency contraceptive pill (ECP) containing levonorgestrel is dispensed without a prescription in Spain since 2009. An easy access could diminish unwanted pregnancies; however, there is a risk of misuse and, in any case, of developing some adverse events. The aim of the present study is to further learn the adverse effects of this ECP.

Carpal Tunnel Syndrome Associated with Oral Bisphosphonates. A Population-Based Cohort Study.

Background Bisphosphonates are widely used to prevent osteoporotic fractures. Some severe musculoskeletal reactions have been described with this medication; among them, some cases of carpal tunnel syndrome. Thus, the aim of this study was to explore whether bisphosphonates may be associated with this syndrome. Methods A cohort study was conducted to compare exposed to unexposed women; the exposed group was that composed of women having received at least one prescription of an oral bisphosphonate. For the purpose, we used information from The Health Improvement Network (THIN) database. The outcome of interest was defined as those women diagnosed with carpal tunnel syndrome. A survival analysis was performed; the Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals, and to adjust for identified confounding variables. Results Out of a sample of 59,475 women older than 51 years, 19,825 were treated with bisphosphonates during the period studied. No differences in age distribution or mean follow-up time were observed between the two groups in comparison. Overall, there were 572 women diagnosed with carpal tunnel syndrome, 242 (1.2%) in the group exposed to bisphosphonates, and 330 (0.8%) in the unexposed. An adjusted hazard ratio of developing carpal tunnel syndrome of 1.38 (95%CI, 1.15–1.64) was found for women exposed to bisphosphonates; no significant changes in the hazard ratios were found when considering different levels of bisphosphonate exposure. Conclusions An increased risk of carpal tunnel syndrome is associated with the use of bisphosphonates in postmenopausal women.